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Biomedical subjects

M Keegan

Publications and source records attributed to M Keegan.

At least 19 recordsLinked to original sources
PubMed2004

Potentially reversible autoimmune limbic encephalitis with neuronal potassium channel antibody.

OBJECTIVES: To describe the clinical features and coexisting serum autoantibodies in seven patients with encephalitis associated with autoantibodies to alpha-dendrotoxin-sensitive voltage-gated potassium channels (VGKCs), and to compare this disorder with other autoimmune encephalopathies. METHODS: Clinical information was obtained from a retrospective review of medical records and telephone interviews. All autoantibody testing was performed in a single laboratory. RESULTS: The seven patients were examined for subacute cognitive and behavioral changes. Seizures, usually temporal-onset complex partial type, were documented in six patients, and all seven patients had EEG abnormalities. None had symptoms or signs of neuromuscular hyperexcitability. One described hypersalivation. Four patients had additional autoantibody markers of neurologic autoimmunity (muscle acetylcholine receptor, striational, P/Q-type calcium channel, or GAD65), and two had thyroperoxidase antibodies. Two patients had a history of cancer: one had active prostate adenocarcinoma, and the second had a remote history of tongue carcinoma. Cranial MRI demonstrated mesial temporal lobe abnormalities in all patients. One patient improved spontaneously, and six were treated with IV methylprednisolone. Three improved remarkably with treatment. At follow-up evaluation, one had no cognitive deficits, four had mild persistent short-term memory dysfunction, and two had persistent disabling behavioral deficits. CONCLUSIONS: Voltage-gated potassium channel antibodies are a valuable serologic marker of a potentially reversible autoimmune encephalopathy. The neurologic manifestations of this disorder are indistinguishable from paraneoplastic limbic encephalitis but are distinct from Morvan syndrome and Hashimoto encephalopathy.

Adult↗
PubMed2004

Audit of the management of convulsive status epilepticus in children: the need for a uniform treatment strategy.

We conducted a two-year prospective audit to review the paediatric management of Convulsive Status Epilepticus (CSE) in Ireland. Our audit showed that there is considerable variability in the management of CSE in this country. In order to provide optimum care for this potentially life-threatening condition a uniform management strategy is required. We propose a protocol for the treatment of CSE, which should ensure uniform management and optimum care and also provide a template for further study and audit of this important disorder.

Anticonvulsants↗
PubMed2002

Plasma exchange for severe attacks of CNS demyelination: predictors of response.

The authors reviewed 59 consecutive patients treated with plasma exchange (PE) for acute, severe attacks of CNS demyelination at Mayo Clinic from January 1984 through June 2000. Most patients had relapsing-remitting MS (n = 22, 37.3%), neuromyelitis optica (NMO) (n = 10, 16.9%), and acute disseminated encephalomyelitis (n = 10, 16.9%). PE was followed by moderate or marked functional improvement in 44.1% of treated patients. Male sex (p = 0.021), preserved reflexes (p = 0.019), and early initiation of treatment (p = 0.009) were associated with moderate or marked improvement. Successfully treated patients improved rapidly following PE, and improvement was sustained.

Adolescent↗
PubMed2001

Islets in alginate macrobeads reverse diabetes despite minimal acute insulin secretory responses.

BACKGROUND: Encapsulation of islets has been widely investigated as a treatment for diabetes. The characteristics and dynamics of insulin secretion by encapsulated islets in response to glucose and other secretagogues are not well understood. METHODS: In our study, macroencapsulated syngeneic islets at 3-4 wk after transplantation were studied for insulin release in response to i.v. glucose (hyperglycemic clamps at 250 or 350 mg/dl plasma glucose), arginine (i.v. bolus, 100 mg/kg), glucagon-like peptide-1 (i.v. infusion for 20 min, 2.2 pmol/kg/min), and meal challenge. Syngeneic islets (6000 islets) were encapsulated in alginate macrobeads (2-3 mm diameter) with or without poly-L-lysine coating and transplanted into the peritoneal cavity of STZ-diabetic Lewis rats. Normal (nontransplanted) and diabetic Lewis rats transplanted with "naked" islets under the kidney capsule served as controls. RESULTS: Animals transplanted with macrobeads displayed subnormal insulin responses to glucose, arginine, and glucagon-like peptide-1 despite achieving normoglycemia faster than animals with renal subcapsular islet transplants. Plasma insulin responses to meal challenges were blunted in animals with macrobeads resulting in increased plasma glucose excursions. CONCLUSIONS: We conclude that, after transplantation into diabetic Lewis rats, macroencapsulated islets have significantly impaired insulin secretion despite achieving normal fed glycemic levels.

Alginates↗
PubMed2001

Increase in beta-cell mass in transplanted porcine neonatal pancreatic cell clusters is due to proliferation of beta-cells and differentiation of duct cells.

A 20-fold increase in beta-cell mass has been found after transplantation of porcine neonatal pancreatic cell clusters (NPCCs). Here the mechanisms leading to this increased beta-cell mass were studied. NPCCs (4000 islet equivalents) generated after 8 days culture of digested neonatal pig pancreas were transplanted beneath the renal capsule of streptozotocin (STZ) diabetic and normoglycemic nude mice. Grafts were removed at 10 days, 6 weeks, and 20 weeks after transplantation for immunostaining and insulin content. Proliferation of beta-cells and duct cells was assessed morphometrically using double immunostaining for Ki-67 with insulin or cytokeratin 7 (CK7). Graft maturation was assessed with double immunostaining of CK7 and insulin. Apoptosis was determined using propidium iodide staining. beta-cell proliferation in NPCCs was higher after 8 days of culture compared with that found in neonatal pig pancreas. After transplantation, beta-cell proliferation remained high at 10 days, decreased somewhat at 6 weeks, and was much lower 20 weeks after transplantation. Diabetic recipients not cured at 6 weeks after transplantation had significantly higher beta-cell proliferation compared with those cured and to normoglycemic recipients. The size of individual beta-cells, as determined by cross-sectional area, increased as the grafts matured. Graft insulin content was 20-fold increased at 20 weeks after transplantation compared with 8 days cultured NPCCS: The proliferation index of duct cells was significantly higher in neonatal pig pancreas than in 8 days cultured NPCCs and in 10-day-old grafts. The incidence of apoptosis in duct cells appeared to be low. About 20% of duct cells 10 days post transplantation showed costaining for CK7 and insulin, a marker of protodifferentiation. In conclusion, the increase in beta-cell mass after transplantation of NPCCs is due to both proliferation of differentiated beta-cells and differentiation of duct cells into beta-cells.

Animals↗
PubMed1999

Use of single-frequency bioimpedance at 50 kHz to estimate total body water in patients with multiple organ failure and fluid overload.

OBJECTIVE: To investigate the relationship between single-frequency bioimpedance at 50 kHz (both total body impedance and segmental impedance) and total body water, measured using tritiated water in the presence of the severe fluid retention seen in multiple organ failure. DESIGN: Prospective, controlled study. SETTING: General intensive care unit. SUBJECTS: Twenty patients with multiple organ failure and 30 normal volunteers, of whom a subgroup of ten had total body water measured. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total body water and total and segmental bioimpedance values at 50 kHz were measured using tritiated water and a Holtain body composition analyzer in 20 patients with multiple organ failure and in ten normal volunteers. An additional 20 normal volunteers also had segmental and total body impedance measured. There was no difference in the linear regression lines constructed for the patients and the volunteers, but the SEM in the patients (7.6 L) was four times that seen in the normal subjects (1.9 L). In a further seven patients, the impedance technique overestimated the change in total body water, deduced from acute changes in weight, by between 0% and 46% (median, 12%). In the patients, who were supine, the knee-ankle segment contributed significantly more to total body impedance than it did in the normal volunteers (42.5% vs. 34.4%; p < .001), who were upright and mobile immediately before the measurement. CONCLUSIONS: Although single-frequency bioimpedance does give an indication of total body water and change in total body water, it is neither precise nor accurate enough to be the sole guide to fluid therapy. The proportion of total impedance contributed by the knee-ankle segment, which contains relatively little water, was significantly greater in the patients than in the controls, probably reflecting better drainage of fluid from the lower limb in the supine position.

Adult↗
PubMed1998

Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis.

Two cysteine protease families (caspase and calpain) participate in apoptosis. Here we report that the endogenous calpain inhibitor calpastatin is fragmented by caspase(s) to various extents during early apoptosis in two cell types. In anti-fas or staurosporine-treated Jurkat T-cells, the high-molecular-weight form (HMW) of calpastatin (apparent Mr 110 K) was extensively degraded to immunoreactive fragments of Mr 75 K and 30 K In apoptotic SH-SY5Y human neuroblastoma cells, HMW calpastatin was degraded to a major immunoreactive fragment of 75 K. In both cell types, fragmentation of HMW calpastatin was blocked by a caspase-specific inhibitor carbobenzoxy-Asp-CH2OC(O)-2,6-dichlorobenzene. In vitro translated HMW calpastatin was sensitive to proteolysis by recombinant caspase-1, -3, and -7. By contrast, in vitro translated LMW calpastatin (which lacks domains L and I) was cleaved into multiple fragments only by caspase-1 and was relatively resistant to caspase-3, -7, and other caspases tested. Consistently with that, purified erythroid LMW calpastatin was also highly susceptible to caspase-1 digestion. Recombinant human calpastatin spanning domain I through III (CAST(DI-III)) was found cleaved by caspase-1 at at least three sites, located in either the A or the C helix of domains I and III (ALDD137*L, LSSD203*F and ALAD404*S), while only a single site (ALDD137*L) was cleaved by caspase-3. These findings suggest that both HMW and LMW calpastatins are more vulnerable to caspase-1 than to caspase-3. Surprisingly, both erythroid LMW calpastatin and recombinant CAST(DI-III) fragmented by caspase-1 suffered only a less than twofold reduction of inhibitory activity toward calpain. We propose that the proteolysis of calpastatin in early apoptosis might have yet unidentified effects on the cross-talk between the two protease systems.

Apoptosis↗
PubMed1995

Catalysis by hamster dihydroorotase: zinc binding, site-directed mutagenesis, and interaction with inhibitors.

Hamster dihydroorotase is the central domain of a trifunctional protein which has been cloned, overexpressed, and purified from Escherichia coli. Using the cDNA encoding the dihydroorotase domain, site-directed mutagenesis of amino acid residues conserved between species has enabled identification of three ligands of zinc at the catalytic site as His15, 17 and 158. The underlined amino acids of the nonapeptide sequence Ile12-Asp13-Val14-His15-Val16-His17- Leu18-Arg19-Glu20 from hamster are conserved between dihydroorotases from 8 species. It is proposed that the residues Asp13-His15-->ZnII form a triad at the active site and that Arg19, for which even the conservative mutation Arg19-->Lys yields an inactive enzyme, is involved in substrate binding. Site-directed mutagenesis of the conserved His186-->Ala yielded a mutant enzyme with a reduced affinity for 65Zn2+. The Km for dihydroorotate (DHO) increased from 4.0 to 11 microM, while the Vmax decreased from 1.2 to 0.53 mumol min-1 (mg of protein)-1, implicating this residue in only a minor way with binding of DHO and in catalysis. The mutation Asp230-->Glu resulted in a 14-fold increase in Km and a 16-fold decrease in Vmax, indicating involvement of this conserved residue in both binding and catalysis. The mutation Lys239-->Gly increased the Km for DHO 110-fold with a 2-fold increase in Vmax, suggesting that this residue may form a hydrogen bond with the substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Manipulation of substrate utilization with somatostatin in patients with secondary multiple organ dysfunction syndrome.

OBJECTIVES: To determine whether glucose utilization and metabolic substrate (glucose and fat) oxidation could be manipulated in patients with secondary multiple organ dysfunction syndrome. DESIGN: Prospective study. SETTING: Intensive care units (ICU) of two university hospitals. PATIENTS: Eight adults free of hepatic disease and hemodynamically stable at the time of study, but with failed respiratory and gastrointestinal systems, who thus required mechanical ventilation and intravenous nutrition. INTERVENTIONS: Patients were infused with 20% dextrose through central venous cannulas at rates that increased and maintained (clamped) their plasma glucose concentration at 216 mg/dL (12 mmol/L) for 3 hrs. Somatostatin was infused continuously during the second and third hours of the clamp to reduce plasma concentrations of endogenous insulin and glucagon. Exogenous insulin was administered together with somatostatin during the third hour to restore basal insulin concentrations. Energy expenditure was measured by indirect calorimetry throughout the study and blood samples were withdrawn regularly for determination of metabolite and hormone concentrations. Main statistical comparisons were made between the baseline data (first hour of the study) and data collected during the second and third hours of the clamp. MEASUREMENTS AND MAIN RESULTS: Plasma glucagon concentrations were reduced by nearly 50% (p < .05) toward the end of the study, whereas no significant changes in plasma concentrations of cortisol or growth hormone occurred. Energy expenditure did not change significantly at any time during the clamp procedure. Glucose utilization (6.1 mg/kg/min [34 mumol/kg/min]) during the first hour of the hyperglycemic clamp, decreased by 53% (p < .05) with the infusion of somatostatin during the second hour of the clamp. However, once exogenous insulin was infused during the third hour, glucose utilization increased by 55% (p < .05) when compared with the baseline (hour 1) rate. Glucose oxidation was nearly doubled during the third hour of the study when compared with oxidation rates during the first and second hours. Fat oxidation decreased steadily during the 3-hr clamp. CONCLUSIONS: Glucagon has a significant inhibitory effect on glucose utilization during intravenous glucose infusion in the multiple organ dysfunction syndrome patient. Pharmacologic intervention with somatostatin and insulin (physiologic dose) can facilitate glucose utilization and oxidation in these patients. Further investigations are needed to determine whether long-term alteration of glucose and fat metabolism would be beneficial in the patient with secondary multiple organ dysfunction syndrome.

Aged↗
PubMed1995

Energy metabolism during CAPD: a controlled study.

Abnormalities of energy metabolism may exacerbate the high prevalence of protein-calorie malnutrition and inadequate calorie intake in continuous ambulatory peritoneal dialysis (CAPD) patients, leading to further nutritional depletion. In a controlled study, using indirect calorimetry, we evaluated oxygen consumption (VO2), CO2 production, resting energy expenditure, and respiratory exchange ratio (RER) in 12 CAPD patients at rest and during a standard CAPD exchange and in 11 healthy nonuremic control patients. In addition, we investigated the influence of nutritional status and dialysis adequacy on energy metabolism in the CAPD group. There was no significant difference in resting energy parameters between the two groups. Unlike the control group, blood glucose and RER were maintained during prolonged fasting in the CAPD patients. This observation indicates that all the absorbed glucose was used as a metabolic fuel preventing fat oxidation. There was no significant relationship between energy expenditure and dialysis adequacy. There was no significant relationship between nutritional state (including energy intake) and energy expenditure despite evidence of malnutrition in 41% of the patients. If maintenance of "normal levels" of energy expenditure occurs in dialysis patients with suboptimal calorie intake (especially with evidence of protein-calorie malnutrition), this inability to conserve energy may act as an additional risk factor for ongoing malnutrition.

Aged↗
PubMed1994

Recovery after oral surgery with halothane, enflurane, isoflurane or propofol anaesthesia.

We have compared the recovery characteristics of four different techniques for maintenance of anaesthesia in 99 day-case patients admitted for oral surgery. All patients received propofol for induction of anaesthesia followed by halothane, enflurane, isoflurane or propofol infusion for maintenance of anaesthesia. Each patient was subjected to a battery of psychometric tests which included Spielberger state, trait, mood stress and mood arousal questionnaires, Maddox-Wing test and five-choice serial reaction time. All tests were performed before operation and at 0.5, 1, 2, 4, 24 and 48 h after operation. Performance in the reaction time test decreased significantly in the immediate postoperative period, returning almost to preoperative values by 4 h. However, only those patients who received enflurane or propofol had returned to their performance level before surgery by 4 h, although all four groups had achieved this target by 24 h. There was a further improvement in performance at 48 h. Anxiety and stress were high before surgery and decreased rapidly in the postoperative period. The Maddox-Wing test demonstrated a significant impairment in performance in the first 1 h after surgery, which returned to normal by discharge at 4 h. There were no significant differences between the four groups in these latter tests.

Adult↗
PubMed1994

National survey of state trauma registries--1992.

Registries, such as those for oncology, have demonstrated usefulness in collating information. Trauma care can be improved through the accumulation of local, regional, and state trauma statistics. The efforts to develop a National Trauma Registry in the United States are still in their infancy. A four-page survey questionnaire was returned by each of the 50 State Emergency Medical Services (EMS) Directors, as well as the EMS Directors of the District of Columbia and five American possessions, to evaluate the status of state trauma registries in the United States. In 1992, 24 (48%) states had a registry. Development costs average $101,107 and annual maintenance costs averaged $72,105. An average of 1.7 full-time equivalents (FTE) was necessary to maintain the registry. Fourteen (58%) states have effected legislation through the registry. Trauma prevention has been promoted in nine (38%) states and a decrease in mortality recognized through the registry in five (21%) states. Trauma registries are labor intensive and expensive but are effective in decreasing morbidity and mortality. The need for a National Trauma Registry incorporating and comparing data from health care facilities around the United States and its possessions has the potential of improving trauma health care.

Data Collection↗
PubMed1993

Vaginal stenosis and sexual function following intracavitary radiation for the treatment of cervical and endometrial carcinoma.

PURPOSE: This study was designed to document the incidence and degree of vaginal stenosis, sexual activity, and satisfaction in women treated with intracavitary radiation therapy for cervical or endometrial carcinoma. METHODS AND MATERIALS: The incidence of vaginal stenosis in 90 patients treated for either cervical carcinoma (n = 42) or endometrial carcinoma (n = 48) with standard doses of intracavitary radiation from 1989 to 1992 with at least 6 months follow-up was recorded. Vaginal length was measured using a modified vaginal dilator calibrated in centimeters. Semistructured patient interviews documented pretreatment and posttreatment sexual activity and sexual satisfaction. RESULTS: Vaginal length was found to be dependent on diagnosis (cervical vs. endometrial), stage (I vs. II/III), and follow-up interval (6-12 months, 12-24 months, and > 24 months). Slightly more women reported sexual activity post vs. pretreatment (31% active pretreatment vs. 43% active posttreatment). However, 22% of women reported a decrease in sexual frequency and 37% reported a decrease in sexual satisfaction. Reports for all parameters were worse for women treated for cervical carcinoma vs. women treated for endometrial carcinoma with the exception of dyspareunia. CONCLUSION: High-dose radiation for either cervical or endometrial carcinoma at standard doses with or without hysterectomy can cause a decrease in vaginal length as compared to the normal vaginal length of 8 to 9 cm documented by Masters and Johnson. Women treated with intracavitary implants remained as sexually active postimplant as preimplant, however, coital frequency and sexual satisfaction decreased while dyspareunia increased. The decrease in vaginal length may explain in part the decrease in sexual satisfaction but cause and effect have not been established.

Adenocarcinoma↗
PubMed1992

Management of blunt hepatic injuries.

Sixty-three consecutive patients with blunt hepatic trauma were examined. Twenty-four patients underwent immediate operation, and 39 patients were evaluated by computed tomography (CT), of whom 17 underwent operation. Ten patients had no hepatic abnormalities on CT and had operations for associated injuries. Liver injuries were noted in the remaining seven patients, but CT underestimated the injury in four patients. A large hemoperitoneum was present in all seven patients by CT, and the average transfusion was 10 U during initial resuscitation. Twenty-two patients with grade I to III injuries and a small to moderate hemoperitoneum were managed nonoperatively. Six of these patients had transfusions during resuscitation. Only one patient received more than 2 U. There were no deaths and no major complications related to the liver injury. Most patients had repeat CT at 1 week, which demonstrated stable or improving injuries. CT may underestimate the degree of liver injury. Nonoperative management is appropriate in stable patients with grade I to III injuries and a small to moderate hemoperitoneum. These patients should require no more than 2 U of blood, and repeat scans should demonstrate a stable injury.

Accidents, Traffic↗
PubMed1990

Usefulness of an antireflux valve in the intensive care unit.

The Keith Antireflux Valve (ARV) is a one-way valve placed on the sump port of a double-lumen NG tube. ARV use in critically injured patients significantly prevents reflux through the sump port and decreases the incidence of both patient gown and linen change and NG tube repositioning. There is no evidence to indicate that the ARV may lead to malfunction of the NG tube, aspiration, or gastric dilation. The cost savings in materials and nursing time are significant.

Humans↗